Evaluation of the degree of rate control via automatic differentiation

The degree of rate control (DRC) quantitatively identifies the kinetically relevant (sometimes known as rate-limiting) steps of a complex reaction network. This concept relies on derivatives which are commonly implemented numerically, for example, with finite differences (FDs). Numerical derivatives are tedious to implement, and can be problematic, and unstable or unreliable. In this study, we demonstrate the use of automatic differentiation (AD) in the evaluation of the DRC. AD libraries are increasingly available through modern machine learning frameworks. Compared with the FDs, AD provides solutions with higher accuracy with lower computational cost. We demonstrate applications in steady-state and transient kinetics. Furthermore, we illustrate a hybrid local-global sensitivity analysis method, the distributed evaluation of local sensitivity analysis, to assess the importance of kinetic parameters over an uncertain space. This method also benefits from AD to obtain high-quality results efficiently.     

Cyanogenic,carotenoids and protein composition in leaves and roots across seven diverse population found in the world cassava germplasm collection at CIAT,Colombia

The objective of this study was to characterise the nutritional potential of leaves and identify a diversity centre with low cyanide and high nutrient content among 178 Latin American cassava genotypes. This field-based collection represents the seven diversity centres, held at The International Center for Tropical Agriculture (CIAT Palmira, Colombia) by the Cassava Program. The cyanide, all-trans-β-carotene and lutein concentrations in cassava leaves ranged from 346 to 7484 ppm dry basis (db), from 174–547 μg g⁻¹ db and 15–181 μg g⁻¹ db, respectively. Cassava leaves also showed significant levels of essential amino acids leucine, lysine, phenylalanine, valine and threonine, and average total protein content of 26.24 g 100 g⁻¹ db. Among seven diversity centres, South American rainforest group showed low cyanide and high carotene content in leaves. In addition, VEN77 and PAN51 genotypes stood out for having low cyanide in leaves and roots and high carotene in leaves. This genetic diversity can be used to select high potential progenitors for breeding purposes.     

Biocatalytic Alkylation Cascades: Recent Advances and Future Opportunities for Late-Stage Functionalization

This Concept article describes the latest developments in the emerging area of late-stage biocatalytic alkylation. Central to these developments is the ability to efficiently prepare S-adenosyl methionine (SAM) cofactor analogues and couple this with enzymatic alkyl transfer. Recent developments in the enzymatic synthesis of SAM cofactor analogues are summarized first, followed by their application as alkyl transfer agents catalyzed by methyltransferases (MTases). Second, innovative methods to regenerate SAM cofactors by enzymatic cascades is reported. Finally, future opportunities towards establishing a generalized platform for late-stage alkylation are described.     

Three‐dimensional color prediction modeling of single‐ and double‐layered woven fabrics

In this research, the three‐dimensional structural and colorimetric modeling of three‐dimensional woven fabrics was conducted for accurate color predictions. One‐hundred forty single‐ and double‐layered woven samples in a wide range of colors were produced. With the consideration of their three‐dimensional structural parameters, three‐dimensional color prediction models, K/S‐, R‐, and L*a*b*‐based models, were developed through the optimization of previous two‐dimensional models which have been reported to be the three most accurate models for single‐layered woven structures. The accuracy of the new three‐dimensional models was evaluated by calculating the color differences ΔL*, ΔC*, Δh°, and ΔE_CMC(2:1) between the measured and the predicted colors of the samples, and then the error values were compared to those of the two‐dimensional models. As a result, there has been an overall improvement in color predictions of all models with a decrease in ΔE_CMC(2:1) from 10.30 to 5.25 units on average after the three‐dimensional modeling.     

Annular‐ring slot antenna designs with circular polarization radiation

The design of a microstrip‐fed annular‐ring slot antenna (ARSA) with circular polarization (CP) radiation is initially studied. To obtain CP radiation with broad 3‐dB axial ratio (AR) bandwidth that can cover the WiMAX 2.3 GHz (2305–2320 MHz, 2345–2360 MHz) and WLAN 2.4 GHz (2400–2480 MHz) bands, a novel technique of extending an inverted L‐shaped slot from the bottom section of the annular‐ring is proposed. To suppress the harmonic modes induced by the CP ARSA, the technique of integrating a defected ground structure into the annular‐ring slot is further introduced. From the measured results, 10‐dB impedance bandwidth and 3‐dB AR bandwidth of 44.86 and 9.68% were achieved by the proposed harmonic suppressed CP ARSA. Furthermore, average gain and radiation efficiency of ～4.7 dBic and 71%, respectively, were also exhibited across the bands of interest. © 2014 Wiley Periodicals, Inc. Int J RF and Microwave CAE 25:337–345, 2015.     

Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.